Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial).

INTRODUCTION: Despite many technological advances, the diagnostic yield of bronchoscopic peripheral lung nodule analysis remains limited due to frequent mispositioning. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic feedback on needle positioning, potentially improving the sampling location and diagnostic yield. Previous studies have defined and validated nCLE criteria for malignancy, airway and lung parenchyma. Larger studies demonstrating the effect of nCLE on diagnostic yield are lacking. We aim to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared with conventional bronchoscopy without nCLE. METHODS AND ANALYSIS: This is a parallel-group randomised controlled trial. Recruitment is performed at pulmonology outpatient clinics in universities and general hospitals in six different European countries and one hospital in the USA. Consecutive patients with a for malignancy suspected peripheral lung nodule (10-30 mm) with an indication for diagnostic bronchoscopy will be screened, and 208 patients will be included. Web-based randomisation (1:1) between the two procedures will be performed. The primary outcome is diagnostic yield. Secondary outcomes include diagnostic sensitivity for malignancy, needle repositionings, procedure and fluoroscopy duration, and complications. Pathologists will be blinded to procedure type; patients and endoscopists will not. ETHICS AND DISSEMINATION: Primary approval by the Ethics Committee of the Amsterdam University Medical Center. Dissemination involves publication in a peer-reviewed journal. SUPPORT: Financial and material support from Mauna Kea Technologies. TRIAL REGISTRATION NUMBER: NCT06079970.

The evolving role of interventional cytopathology from thyroid FNA to NGS: Lessons learned at Federico II University of Naples.

Fine-needle aspiration (FNA) guided by ultrasound (US) has emerged as a highly precise diagnostic method for managing thyroid nodules, significantly diminishing unnecessary surgeries. The effectiveness of US-guided FNA is high when a single specialist performs the FNA procedure and the microscopy. This paradigm has paved the way for the evolution of interventional cytopathology, a specialist with a pivotal role in the preoperative diagnostic process, encompassing patient history review, clinical examination, FNA execution under US guidance, preparation, and microscopic interpretation of cytological samples. As the landscape of precision medicine unfolds, molecular testing assumes greater importance in thyroid cytopathology, particularly in refining the risk of malignancy for indeterminate nodules. The updated Bethesda classification system underscores the clinical significance of molecular tests, emphasizing their role in refining diagnostic accuracy. With this evolving landscape, interventional cytopathologists must adapt by acquiring expertise in molecular technologies and addressing ongoing challenges in workflow harmonization and optimization. This paper delves into our decade-long experience as interventional cytopathologists, focusing on recent endeavours to ensure adequate samples not only for microscopic diagnosis but also for molecular testing. Additionally, here we review the challenges of integrating next-generation sequencing (NGS) technology into clinical practice, highlighting the importance of integrating clinically meaningful molecular data into comprehensive molecular cytology reports.

Serum cholesterol levels are inversely associated with the risk of malignancy in subjects with Bethesda category IV thyroid nodules.

INTRODUCTION: Some epidemiological data suggest that there may be an inverse relationship between cholesterol levels and the risk of thyroid cancer in the overall population. The present study was aimed to evaluate the lipid profile specifically in subjects with Bethesda category IV thyroid nodules, and compare whether there were any differences between those with benign and malignant nodules. METHODS: Single-centre, retrospective study on 204 subjects treated by partial or total thyroidectomy for excision of a Bethesda category IV thyroid nodule, who had undergone a blood lipid profile test in the 12 months prior to surgery. In addition to lipid measures, other demographic, clinical, biochemical and ultrasound data were collected. RESULTS: Seventy-five subjects (36.8%) were diagnosed with thyroid carcinoma in the definitive histopathological examination. Patients with thyroid cancer had lower levels of total cholesterol, LDL-cholesterol and non-HDL-cholesterol than subjects with benign thyroid diseases. There were no differences in HDL-cholesterol, triglycerides or total cholesterol/HDL-cholesterol ratio. There were no differences either between groups in other clinical, biochemical and ultrasound variables, including the use of lipid-lowering drugs. In multivariate analysis, only LDL-cholesterol was independently associated with malignancy. Subjects with follicular carcinoma showed the lowest cholesterol levels, while those with papillary carcinoma had intermediate values between the group with follicular carcinoma and the group with benign thyroid diseases. CONCLUSIONS: In subjects with cytologically indeterminate Bethesda category IV thyroid nodules, levels of total cholesterol, non-HDL-cholesterol and, particularly, LDL-cholesterol are lower among those with malignant nodules.

Areca palm velarivirus 1 infection caused disassembly of chloroplast and reduction of photosynthesis in areca palm.

The expansion of betel palm cultivation is driven by rising demand for betel nut, yet this growth is accompanied by challenges such as decreased agricultural biodiversity and the spread of infectious pathogens. Among these, Yellow Leaf Disease (YLD) emerges as a prominent threat to betel palm plantation. Areca Palm Velarivirus 1 (APV1) has been identified as a primary causative agent of YLD, precipitating leaf yellowing, stunted growth, and diminished yield. However, the precise mechanisms underlying APV1-induced damage remain elusive. Our study elucidates that APV1 infiltrates chloroplasts, instigating severe damage and consequential reductions in chlorophyll a/b and carotene levels, alongside notable declines in photosynthetic efficiency. Moreover, APV1 infection exerts broad regulatory effects on gene expression, particularly suppressing key genes implicated in chloroplast function and photosynthesis. These disruptions correlate with growth retardation, yield diminishment, and compromised nut quality. Intriguingly, the paradoxical destruction of the host's photosynthetic machinery by APV1 prompts inquiry into its evolutionary rationale, given the virus's dependence on host resources for replication and proliferation. Our findings reveal that APV1-induced leaf yellowing acts as a beacon for transmission vectors, hinting at a nuanced "host-pathogen-vector co-evolutionary" dynamic.

Implementation of the Milan System for Reporting Salivary Gland Cytology: A Two-Year Outcome Cytopathology Data of a Tertiary Care Center.

OBJECTIVE: In 2015, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was implemented to eliminate overlapping and disparate morphologies in salivary gland lesions. This approach helps track diagnostic findings, describe the risk of malignancy for each group, and advance therapy based on the results. The research aimed to classify fine-needle aspiration (FNA) smears, analyze malignancy risk, correlate cytology with histological diagnosis, and reduce unnecessary surgeries. METHODOLOGY: We evaluated 217 individuals using FNA, classified their conditions using the Milan System, and followed up on 149 cases through histopathology. Both the risk of malignancy in each cluster and the total risk of malignancy were noted. RESULTS: The most recent studies, as reported by the MSRSGC, found almost universal agreement about this grouping. The FNA cytopathology test demonstrated a sensitivity of 75% for identifying salivary gland abnormalities and a specificity of 93.16%. The findings indicated that the test had an accuracy of 89.66%, with a positive predictive value of 72.41% and a negative predictive value of 93.97%. CONCLUSION: The MSRSGC offers a standardized technique for examining the results and assists the physician in determining the treatment plan that will be most beneficial.

Evaluating Diagnostic Clarity: The Comparative Efficacy of BlueStain in Serous Effusion Cytology under the International System for Reporting Serous Fluid Cytopathology Reporting Framework.

Serous effusion cytology is a pivotal diagnostic and staging tool in clinical pathology, valued for its simplicity and cost-effectiveness. Staining techniques such as Giemsa and Papanicolaou are foundational, yet the search for rapid and efficient alternatives continues. Our study assesses the efficacy of an in-house-developed BlueStain, a toluidine blue variant, within the International System for Reporting Serous Fluid Cytopathology (TIS), aiming to optimize diagnostic clarity and resource use. MATERIALS AND METHODS: This section provides details on the cohort of 237 patients with serous effusions, the ethical approval process, sample collection, and staining procedures with BlueStain, Papanicolaou, and Giemsa. It also describes the microscopic evaluation criteria, scoring system, and statistical methods used to compare the stains. RESULTS: BlueStain demonstrated notable performance, particularly in identifying malignant cells, presenting a competitive alternative to the Papanicolaou stain, which, despite higher quality indices in other categories, requires more resources and time. The study revealed that BlueStain might offer a valuable balance between quality and efficiency, especially in cases where rapid diagnostic turnaround is essential. CONCLUSIONS: Our findings suggest that BlueStain is a viable staining method in the context of serous effusions, capable of providing detailed cytomorphological analysis. While traditional stains hold their place for their established diagnostic clarity, BlueStain offers a rapid and resource-optimized alternative. The absence of definitive diagnostic criteria in the atypical category and the inherent sample heterogeneity underscores the necessity for adaptable staining methods like BlueStain. The study highlights the potential trade-offs between detail and practicality in staining techniques, advocating for further research into innovative methods that do not compromise diagnostic precision for cost and time efficiency.

Reproducibility assessment of WHO reporting system for pancreaticobiliary cytopathology: A single institution experience.

BACKGROUND: The World Health Organization (WHO) reporting system for pancreaticobiliary cytopathology was released to internationalize the reporting, assisting in correct diagnosis and patient treatment with significant revisions from the previous Papanicolaou Society of Cytopathology (PSC) system. The "neoplastic: benign" and "neoplastic: other" categories have mostly been superseded by two new ones: "pancreatic neoplasia-low-grade" (PaN-low) and "pancreatic neoplasia-high-grade" (PaN-high), which classify intermediate neoplastic lesions based on cytological atypia. We aim to assess the reproducibility and risk of malignancy (ROM) for reporting pancreaticobiliary cytopathology by the WHO system in comparison with the PSC system. MATERIALS AND METHODS: A retrospective study by reviewing archival slides sent for pancreaticobiliary cytological evaluation from June 2021 to June 2023, by two pathologists blinded to each other's findings. Absolute ROM was determined by histopathology/cell block study/clinical follow-up (minimum 6 months)/overtly malignant imaging/metastasis. RESULTS: A total of 332 cases from 329 patients met the inclusion criteria, comprising pancreatic, gallbladder, and biliary lesions. The median patient age was 54 years (range, 14-86 years). The overall sensitivity of the test is 74.9% specificity is 93.2%, positive predictive value of 96.8%, negative predictive value of 57.6%, and a diagnostic accuracy of 81.8%. The absolute ROM for each site in all categories was comparable with that of the published data from the WHO system. CONCLUSION: Our study highlights the reliability of the WHO system for guiding clinical decision-making and patient management in the context of pancreaticobiliary. However, continual efforts among pathologists are essential to maintain consistent accuracy in cytological interpretations.

EUS-FNA diagnosis of pancreatic tophaceous gout: Two rare cases.

We report two patients with pancreatic tophaceous gout diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of presumed cystic mass lesions. The first case involved a patient who had a recent episode of acute pancreatitis 6 months prior, with subsequent imaging concerning for a pseudocyst or mass lesion. The second case involved a patient with epigastric pain associated with a pancreatic head cystic mass and an erroneous original diagnosis of a mucinous pancreatic neoplasm on EUS-FNA. Diff-Quik stained direct smears on fresh material obtained from EUS-FNA of the lesions showed chalky debris with needle shaped negatively birefringent crystals consistent with gout. For the first case, the chalky material was not present on the H&E stained paraffin embedded formalin fixed cellblock slides. The importance of inclusion of cytologic specimen preparations to examine monosodium urate crystals is emphasized.

Validation and implementation of telecytology at an academic medical center using digital cameras and Microsoft Teams software.

INTRODUCTION: Rapid On-Site Evaluation of cytological samples obtained through fine needle aspiration for adequacy is a critical component of a cytology service; however, it imposes a significant time and cost burden for the practicing pathologist and the cytology service. Telecytology enables adequacy assessment by a pathologist remotely, greatly saving time. Telecytology also allows slide preparation and manipulation at the procedure site by an employee with less training requirements, liberating the cytotechnologist to screen cases and perform other laboratory duties - an important aspect to consider during times of cytotechnologist shortages. We propose a telecytology system with a simple setup of a microscope, microscope camera, laptop, and Microsoft Teams software. MATERIALS AND METHODS: We designed a system consisting of a mobile cart, backup battery, microscope, digital camera, and a laptop computer with microscope imaging software and Microsoft Teams software for image transmission. Validation was performed by 4 pathologists making adequacy assessments on randomly selected previously signed out cases using the telecytology system. RESULTS: Our validation of this system demonstrated a greater than 90% concurrence rate between the original adequacy call and the call made by pathologists using the telecytology system - a benchmark used by most, if not all, published validations of similar telecytology systems. In addition, the adequacy assessment concordance rate between select pathologists exceeded 90%. CONCLUSIONS: In summary, our telecytology system provides excellent adequacy services for the clinicians and patients we serve. The Microsoft Teams software is a great tool for transmission of video microscopy. This system will be used with the goal of saving time and increasing efficiency for the cytopathology department.

Risk of malignancy and overall survival associated with the diagnostic categories in the World Health Organization Reporting System for Pancreaticobiliary Cytopathology.

BACKGROUND: The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low-risk/grade (PaN-Low) and pancreaticobiliary neoplasm, high-risk/grade (PaN-High). Low-grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category. METHODS: An institutional pathology database search identified patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow-up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems. RESULTS: In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN-Low, 46.7% for PaN-High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival. CONCLUSIONS: The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN-Low and PaN-High categories and reassigning low-grade malignancies to the malignant category. Analyzing EUS-FNA samples with the WHO system provides critical insights for guiding clinical management.

Cytopathological Features of Extensive Bilateral Pleural Effusions in Metastatic Prostate Cancer: Report of a Rare Case.

We report a rare case of a 59-year-old male with a history of metastatic prostate cancer presenting with acute onset dyspnea due to extensive bilateral pleural effusions. This case highlights the rarity of metastatic prostate cancer with pleural involvement and underscores the importance of accurate diagnosis using cytopathology and immunohistochemical staining.

Deciphering Serous Effusions Using the New International System for Reporting Serous Fluid Cytopathology.

Introduction Serous effusion cytopathology is a minimally invasive, cost-effective procedure and plays a crucial role in diagnosing a spectrum of pathological conditions, ranging from benign to malignant. The International System for Reporting Serous Fluid Cytopathology (ISRSFC) offers a standardized framework for reporting serous effusions, aiding in better communication and clinical decision-making. Aims and objectives This study aimed to categorize effusions using the ISRSFC reporting system. In addition, we sought to estimate the risk of malignancy (ROM) for each diagnostic category and evaluate the diagnostic performance of conventional smear versus cell block techniques. Materials and methods This cross-sectional study was conducted in the Department of Pathology over one year. We applied the ISRSFC criteria to serous effusions and categorized them accordingly. The ROM for each category was assessed with histopathology serving as the gold standard. Then, the diagnostic performance including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy was evaluated using conventional smear and cell block techniques. Results The study included 185 serous effusion cases, with ages ranging from two months to 85 years. The male-to-female ratio was 1.1:1. Most effusions were pleural fluids constituting about 133 cases (71.9%), followed by peritoneal fluids (47 cases, 25.4%) and pericardial fluids (five cases, 2.7%). Among the fluids, four (2.2%) were diagnosed as non-diagnostic (ND), 152 (82.2%) as negative for malignancy (NFM), four (2.2%) as atypia of undetermined significance (AUS), nine (4.8%) as suspicious for malignancy (SFM), and 16 (8.6%) as malignant (MAL). The overall ROM was 25% for ND, 8.5% for NFM, 50% for AUS, 77% for SFM, and 100% for MAL. The sensitivity, negative predictive value (NPV), and diagnostic accuracy were superior when combining conventional smear with the cell block technique. Conclusions Our findings underscore the use of ISRSFC in categorizing effusion samples, assessing the ROM, and guiding clinical management. Moreover, our study highlights the benefits of employing a combined approach using conventional smears and cell blocks for enhanced diagnostic accuracy in serous effusions.

Prognostic role of the updated Kiel classification in canine high-grade T-cell lymphomas.

BACKGROUND: The aim of this study was to determine and describe the prognostic role of the morphological subtype determined according to the updated Kiel classification in dogs with high-grade T-cell lymphomas (HGTCLs) depending on the treatment applied. OBJECTIVES: The HGTCLs were classified into three subtypes according to the updated Kiel classification: pleomorphic mixed (PM), lymphoblastic lymphoma/acute lymphoblastic leukaemia and plasmacytoid (P). The treatment was divided into a palliative therapy (PlT) group and a chemotherapy (ChT) group. METHODS: The study was conducted between 2009 and 2017, and it enrolled 58 dogs in which cytomorphological and immunocytochemistry diagnoses were HGTCL. RESULTS: Overall survival (OS) was significantly longer in the ChT group (median OS-4 months, interquartile range [IQR] from 2 to 8 months) than in the PlT group (median OS-6 weeks, IQR from 1 week to 3 months). In the PlT group, PM subtype and glucocorticosteroids (GCSs) treatment proved significantly and independently linked to longer OS and approximately three-fold lower risk of death during the study period (adjusted hazard ratio [HRadj] = 0.26, confidence interval [CI] 95%: 0.08-0.81; p = 0.020 and HRadj = 0.30, CI 95%: 0.11-0.77; p = 0.013, respectively), although due to small group size, precision of estimations was poor (wide CI 95%). In the ChT group, >7 days elapsing between diagnosis and the beginning of chemotherapy and GCS treatment prior to chemotherapy were significantly associated with lower chance of complete remission (CR; p = 0.034 for both); GCS treatment prior to chemotherapy was significantly associated with shorter OS (p = 0.016); chemotherapy based on the modified CHOP protocol was significantly associated with higher chance of CR (p = 0.034) and longer OS (p = 0.039); and CR was significantly linked to longer OS (p = 0.001). CLINICAL SIGNIFICANCE: The morphological subtype of HGTCL has some prognostic value in dogs treated palliatively (with PM subtype associated with longer OS than P subtype); however, this effect is no longer visible when a dog is treated with chemotherapy.

Automated Analysis of Nuclear Parameters in Oral Exfoliative Cytology Using Machine Learning.

BACKGROUND: As oral cancer remains a major worldwide health concern, sophisticated diagnostic tools are needed to aid in early diagnosis. Non-invasive methods like exfoliative cytology, albeit with the help of artificial intelligence (AI), have drawn additional interest. AIM: The study aimed to harness the power of machine learning algorithms for the automated analysis of nuclear parameters in oral exfoliative cytology. Further, the analysis of two different AI systems, namely convoluted neural networks (CNN) and support vector machine (SVM), were compared for accuracy. METHODS: A comparative diagnostic study was performed in two groups of patients (n=60). The control group without evidence of lesions (n=30) and the other group with clinically suspicious oral malignancy (n=30) were evaluated. All patients underwent cytological smears using an exfoliative cytology brush, followed by routine Hematoxylin and Eosin staining. Image preprocessing, data splitting, machine learning, model development, feature extraction, and model evaluation were done. An independent t-test was run on each nuclear characteristic, and Pearson's correlation coefficient test was performed with Statistical Package for the Social Sciences (SPSS) software (IBM SPSS Statistics for Windows, Version 28.0. IBM Corp, Armonk, NY, USA). RESULTS:  The study found substantial variations between the study and control groups in nuclear size (p<0.05), nuclear shape (p<0.01), and chromatin distribution (p<0.001). The Pearson correlation coefficient of SVM was 0.6472, and CNN was 0.7790, showing that SVM had more accuracy. CONCLUSION: The availability of multidimensional datasets, combined with breakthroughs in high-performance computers and new deep-learning architectures, has resulted in an explosion of AI use in numerous areas of oncology research. The discerned diagnostic accuracy exhibited by the SVM and CNN models suggests prospective improvements in early detection rates, potentially improving patient outcomes and enhancing healthcare practices.

Interobserver Reliability of Milan and Modified Milan System for Reporting Salivary Gland Cytopathology: An Institutional Experience.

Background: In 2018, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published, defining a diagnostic categorization scheme. However, this system of classification was criticized due to its suboptimal diagnostic accuracy and low interobserver reliability. For these reasons, the modified Milan system was recently proposed by a few authors claiming it to be more clinically reliable. The present study aimed to analyze the interobserver reliability of MSRSGC and modified MSRSGC. Methods: A total of 100 salivary gland fine-needle aspirations were reviewed over a 1-year period and classified by two independent observers according to MSRSGC and modified MSRSGC. Interobserver reproducibility was estimated using observed agreement and chance-corrected agreement (Cohen's kappa). Results: An overall chance corrected agreement of 0.37 (fair) was obtained for the original Milan system and 0.41 (moderate) for the modified one. In addition, subcategories of modified MSRSGC performed better than the MSRSGC in terms of interobserver reliability. Conclusion: The present study suggests that modified MSRSGC should be accepted worldwide as the clinical relevance of any categorization scheme requires diagnostic accuracy along with excellent interobserver reproducibility.

Comprehensive Genomic Studies on the Cell Blocks of Pancreatic Cancer.

Pancreatic cancer is one of the deadliest malignancies, characterized by late-stage diagnosis and limited treatment options. Comprehensive genomic profiling plays an important role in understanding the molecular mechanisms underlying the disease and identifying potential therapeutic targets. Cell blocks (CBs), derived from EUS-FNA, have become valuable resources for diagnosis and genomic analysis. We examine the molecular profile of pancreatic ductal adenocarcinoma (PDAC) using specimens obtained from CB EUS-FNA, across a large gene panel, within the framework of next-generation sequencing (NGS). Our findings revealed that over half (55%) of PDAC CB cases provided adequate nucleic acid for next-generation sequencing, with tumor cell percentages averaging above 30%. Despite challenges such as low DNA quantification and degraded DNA, sequencing reads showed satisfactory quality control statistics, demonstrating the detection of genomic alterations. Most cases (84.6%) harbored at least one gene variant, including clinically significant gene mutation variants such as KRAS, TP53, and CDKN2A. Even at minimal concentrations, as long as the extracted DNA is of high quality, performing comprehensive molecular profiling on PDAC samples from cell blocks has remained feasible. This strategy has yielded valuable information about the diagnosis, genetic landscape, and potential therapeutic targets, aligning closely with a precision cytopathology approach.

The World Health Organization Reporting System for Lung Cytopathology-A Review of the First Edition.

The World Health Organization Reporting System for Lung Cytopathology is the first international system that was developed to standardize the reporting of lung cytopathology specimens across all settings of cytopathology practice. The system is composed of five diagnostic categories, which apply to all lung cytopathology specimen types. Each category contains cytomorphologic criteria, an estimated risk of malignancy, and clinical management recommendations. International uniformity in the reporting of lung cytopathology will refine the communication between cytopathologists and clinicians and ultimately improve patient care. Furthermore, standardizing the cytomorphologic criteria for each lesion will improve reproducibility among cytopathologists and highlight areas in lung cytopathology that require further research. The system also provides best practice recommendations for the selection of ancillary tests to aid in the diagnosis of each lesion, or group of lesions, keeping in mind that resources will vary across different practice settings. The goal of this review is to summarize the cytomorphologic criteria, potential diagnostic pitfalls, ancillary testing, estimated risk of malignancy, and clinical management recommendations for each diagnostic category.

Current role of cytopathology in the molecular and computational era: The perspective of young pathologists.

Cytopathology represents a well established diagnostic approach because of its limited cost, reliability, and minimal invasiveness with respect to other methodologies. The evolving complexity of the different classifications systems and the implementation of ancillary techniques to refine the diagnosis is progressively helping in the risk of malignancy stratification, and the adoption of next-generation sequencing techniques contributes to enrich this valuable tool with predictive information, which is always more essential in the tailored medicine era. The recent introduction of digital and computational pathology is further boosting the potentialities of cytopathology, aiding in the interpretation of samples to improve the cost effectiveness of large screening programs and the diagnostic efficiency within intermediate/atypical categories. Moreover, the adoption of artificial intelligence tools is promising to complement molecular investigations, representing a stimulating perspective in the cytopathology field. In this work, the authors tried to summarize the multifaceted nature of this complex and evolving field of pathology, synthesizing the most recent advances and providing the young pathologists' perspective on this fascinating world.

A case of metastatic HPV-related cervical small cell neuroendocrine carcinoma with varying cytomorphology found in cytological specimens of a solid organ transplant recipient.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening.